Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.08.032
Si-Yang Maggie Liu MD, PhD , Molly Siu Ching Li M.B.B.S.
{"title":"Tracking Progression of EGFR Mutation Positive NSCLC From Blood: Is This the Prime Time?","authors":"Si-Yang Maggie Liu MD, PhD , Molly Siu Ching Li M.B.B.S.","doi":"10.1016/j.jtho.2024.08.032","DOIUrl":"10.1016/j.jtho.2024.08.032","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1482-1485"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.09.1378
Alessandra Bearz MD , Monica Schiappacassi PhD
{"title":"EML4-ALK Variants and Co-Occurring TP53 Mutations in a Real-World Treatment Setting: Do They Matter?","authors":"Alessandra Bearz MD , Monica Schiappacassi PhD","doi":"10.1016/j.jtho.2024.09.1378","DOIUrl":"10.1016/j.jtho.2024.09.1378","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1489-1491"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.07.009
Kaushal Parikh MD , Anastasios Dimou MD , Konstantinos Leventakos MD, PhD , Aaron S. Mansfield MD , Mohamed Shanshal MD , Yin Wan MS , Huamao M. Lin PhD , Sylvie Vincent PhD , Jennifer Elliott PhD , Ioana R. Bonta MD
Introduction
Tyrosine kinase inhibitors (TKIs) are first-line treatment options for ALK-positive (ALK+) NSCLC. Factors such as variant allele frequencies (VAFs), EML4-ALK fusion variant, and concurrent TP53 mutations (TP53mt) in circulating tumor DNA (ctDNA) may affect treatment outcomes. We evaluated their effects on time to discontinuation (TTD) of first-line treatment with next-generation ALK TKIs in a real-world setting.
Methods
Adults with advanced or metastatic NSCLC and ctDNA-detected ALK fusion who received first-line next-generation ALK TKI monotherapy were identified in GuardantINFORM. Effects of ALK fusion VAF, EML4-ALK variants, and TP53mt detection on TTD were evaluated.
Results
A total of 307 patients with ALK fusion in baseline ctDNA received first-line alectinib (n = 280), brigatinib (n = 15), lorlatinib (n = 9), or ceritinib (n = 3); 150 patients (49%) had ALK-fusion VAF greater than or equal to 1%. Among 232 patients with EML4-ALK fusions (v1, 50%; v3, 36%), TP53mt co-occurred with v1 in 42 (18%) and v3 in 32 (14%). Patients with VAF less than 1% versus greater than or equal to 1% had a median TTD of 32.2 (95% confidence interval [CI]: 20.7–not estimable [NE]) versus 14.7 months (10.4–19.9; hazard ratio [HR] = 1.57 [95% CI: 1.09–2.26]; p = 0.0146). Median TTD was 13.1 (9.5–19.9) versus 27.6 months (17.3–NE) in patients with versus without TP53mt detected (HR = 1.53 [1.07–2.19]; p = 0.0202) and 20.3 (14.4–NE) versus 11.5 months (7.4–31.1) in patients with v1 versus v3 (HR = 1.29 [0.83–2.01]; p = 0.2641). Patients with TP53mt and v3 had a median TTD of 7.4 months (95% CI: 4.2–31.1).
Conclusion
High ctDNA VAF, EML4-ALK v3, and TP53mt were associated with early discontinuation of first-line ALK TKIs.
{"title":"Impact of EML4-ALK Variants and Co-Occurring TP53 Mutations on Duration of First-Line ALK Tyrosine Kinase Inhibitor Treatment and Overall Survival in ALK Fusion-Positive NSCLC: Real-World Outcomes From the GuardantINFORM database","authors":"Kaushal Parikh MD , Anastasios Dimou MD , Konstantinos Leventakos MD, PhD , Aaron S. Mansfield MD , Mohamed Shanshal MD , Yin Wan MS , Huamao M. Lin PhD , Sylvie Vincent PhD , Jennifer Elliott PhD , Ioana R. Bonta MD","doi":"10.1016/j.jtho.2024.07.009","DOIUrl":"10.1016/j.jtho.2024.07.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Tyrosine kinase inhibitors (TKIs) are first-line treatment options for <em>ALK</em>-positive (<em>ALK</em>+) NSCLC. Factors such as variant allele frequencies (VAFs), <em>EML4-ALK</em> fusion variant, and concurrent <em>TP53</em> mutations (<em>TP53</em>mt) in circulating tumor DNA (ctDNA) may affect treatment outcomes. We evaluated their effects on time to discontinuation (TTD) of first-line treatment with next-generation ALK TKIs in a real-world setting.</div></div><div><h3>Methods</h3><div>Adults with advanced or metastatic NSCLC and ctDNA-detected <em>ALK</em> fusion who received first-line next-generation ALK TKI monotherapy were identified in GuardantINFORM. Effects of <em>ALK</em> fusion VAF, <em>EML4-ALK</em> variants, and <em>TP53</em>mt detection on TTD were evaluated.</div></div><div><h3>Results</h3><div>A total of 307 patients with <em>ALK</em> fusion in baseline ctDNA received first-line alectinib (n = 280), brigatinib (n = 15), lorlatinib (n = 9), or ceritinib (n = 3); 150 patients (49%) had <em>ALK-</em>fusion VAF greater than or equal to 1%. Among 232 patients with <em>EML4-ALK</em> fusions (v1, 50%; v3, 36%), <em>TP53</em>mt co-occurred with v1 in 42 (18%) and v3 in 32 (14%). Patients with VAF less than 1% versus greater than or equal to 1% had a median TTD of 32.2 (95% confidence interval [CI]: 20.7–not estimable [NE]) versus 14.7 months (10.4–19.9; hazard ratio [HR] = 1.57 [95% CI: 1.09–2.26]; <em>p =</em> 0.0146). Median TTD was 13.1 (9.5–19.9) versus 27.6 months (17.3–NE) in patients with versus without <em>TP53</em>mt detected (HR = 1.53 [1.07–2.19]; <em>p =</em> 0.0202) and 20.3 (14.4–NE) versus 11.5 months (7.4–31.1) in patients with v1 versus v3 (HR = 1.29 [0.83–2.01]; <em>p =</em> 0.2641). Patients with <em>TP53</em>mt and v3 had a median TTD of 7.4 months (95% CI: 4.2–31.1).</div></div><div><h3>Conclusion</h3><div>High ctDNA VAF, <em>EML4-ALK</em> v3, and <em>TP53</em>mt were associated with early discontinuation of first-line ALK TKIs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1539-1549"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.07.016
Peter S.N. van Rossum MD, PhD , Nienke Wolfhagen MD , Liselotte W. van Bockel MD , Ida E.M. Coremans MD, PhD , Corine A. van Es MD , Annelies M. van der Geest MD , Katrien E.A. De Jaeger MD, PhD , Barbara Wachters MD , Hans P. Knol MD , Friederike L.A. Koppe MD , Jacqueline Pomp MD, PhD , Bart J.T. Reymen MD , Dominic A.X. Schinagl MD, PhD , Femke O.B. Spoelstra MD, PhD , Caroline J.A. Tissing-Tan MD , Max Peters MD, PhD , Noëlle C.M.G. van der Voort van Zijp MD, PhD , Antoinet M. van der Wel MD , Erwin M. Wiegman MD, PhD , Robin Wijsman MD, PhD , José S.A. Belderbos MD, PhD
Introduction
Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes.
Methods
Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated.
Results
Among 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73).
Conclusions
This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.
简介：立体定向体放射治疗（SBRT立体定向体放射治疗（SBRT）已在 I 期非小细胞肺癌（NSCLC）中发挥了重要作用。临床试验结果可能并不完全适用于实际情况。本研究旨在揭示SBRT治疗的I期NSCLC患者在现实世界中的急性毒性和90天死亡率，并为这些结果建立预测模型：方法：从荷兰肺癌放疗审计（DLCA-R）中收集全国性的前瞻性数据。纳入了2017-2021年接受SBRT治疗的I期NSCLC（cT1-2aN0M0）患者。对急性毒性进行了评估，急性毒性定义为 SBRT 后≤90 天的≥2 级放射性肺炎或≥3 级非血液学毒性。建立了急性毒性和90天死亡率的预测模型，并进行了内部验证：在7279名患者中，平均年龄为72.5岁，21.6%的患者年龄大于80岁。大多数患者为女性（50.7%），WHO评分为0-1分（73.3%），cT1a-b肿瘤（64.6%），主要位于上叶（65.2%）。280名患者（3.8%）出现急性毒性，122名患者（1.7%）90天内死亡。急性毒性的预测因素包括 WHO ≥2、较低的 FEV1 和 DLCO、未经病理确认、中/下叶肿瘤位置、cT1c-cT2a 分期和较高的平均肺剂量（c 统计量为 0.68）。女性性别、WHO ≥2和急性毒性预示着较高的90天死亡率（c统计量为0.73）：这项全国性研究显示，SBRT 治疗的 I 期 NSCLC 患者急性毒性发生率低，90 天死亡率可接受。值得注意的是，高龄并未增加急性毒性或死亡率风险。我们的预测模型性能令人满意，为识别高危患者提供了有价值的工具。
{"title":"Real-World Acute Toxicity and 90-Day Mortality in Patients With Stage I NSCLC Treated With Stereotactic Body Radiotherapy","authors":"Peter S.N. van Rossum MD, PhD , Nienke Wolfhagen MD , Liselotte W. van Bockel MD , Ida E.M. Coremans MD, PhD , Corine A. van Es MD , Annelies M. van der Geest MD , Katrien E.A. De Jaeger MD, PhD , Barbara Wachters MD , Hans P. Knol MD , Friederike L.A. Koppe MD , Jacqueline Pomp MD, PhD , Bart J.T. Reymen MD , Dominic A.X. Schinagl MD, PhD , Femke O.B. Spoelstra MD, PhD , Caroline J.A. Tissing-Tan MD , Max Peters MD, PhD , Noëlle C.M.G. van der Voort van Zijp MD, PhD , Antoinet M. van der Wel MD , Erwin M. Wiegman MD, PhD , Robin Wijsman MD, PhD , José S.A. Belderbos MD, PhD","doi":"10.1016/j.jtho.2024.07.016","DOIUrl":"10.1016/j.jtho.2024.07.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes.</div></div><div><h3>Methods</h3><div>Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated.</div></div><div><h3>Results</h3><div>Among 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73).</div></div><div><h3>Conclusions</h3><div>This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1550-1563"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.08.033
Takashi Kohno PhD, Akifumi Mochizuki MD
{"title":"Response to Letter to the Editor","authors":"Takashi Kohno PhD, Akifumi Mochizuki MD","doi":"10.1016/j.jtho.2024.08.033","DOIUrl":"10.1016/j.jtho.2024.08.033","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Page e69"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.08.010
Shih-Chi Yang MD, Hui-Chin Chang MLS, Shuo-Yan Gau MD, FRSPH
{"title":"Toxicity and Mortality After Stereotactic Body Radiotherapy","authors":"Shih-Chi Yang MD, Hui-Chin Chang MLS, Shuo-Yan Gau MD, FRSPH","doi":"10.1016/j.jtho.2024.08.010","DOIUrl":"10.1016/j.jtho.2024.08.010","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages e70-e71"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.08.015
Shanshan Huang MD, Yanli Chen MD, Renquan Wang MD, Dan Shan MSc
{"title":"Stereotactic Body Radiotherapy Outcomes for Stage I NSCLC: A Call for Enhanced Predictive Modeling and Comprehensive Toxicity Assessment","authors":"Shanshan Huang MD, Yanli Chen MD, Renquan Wang MD, Dan Shan MSc","doi":"10.1016/j.jtho.2024.08.015","DOIUrl":"10.1016/j.jtho.2024.08.015","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages e72-e73"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.jtho.2024.08.038
Weizhen Tang MD, Taihang Liu PhD, Ying-Bo Li PhD
{"title":"Assessing Acute Toxicity and 90-Day Mortality in Stage I NSCLC: A Real-World Appraisal of Stereotactic Body Radiotherapy Outcomes","authors":"Weizhen Tang MD, Taihang Liu PhD, Ying-Bo Li PhD","doi":"10.1016/j.jtho.2024.08.038","DOIUrl":"10.1016/j.jtho.2024.08.038","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages e73-e74"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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